Basic Fibroblast Growth Factor (bFGF) is the basic Fibroblast Growth Factor, and is a broadly presented mitogen, which can promote the effect of proliferation, differentiation and anti-apoptosis of many kinds of cells including tumor cells and vascular endothelial cells by means of autocrine or paracrine. bFGF has various kinds of biological effects, including growth promoting, dividing and differentiating, and it has a strong proliferation promoting effect for fibroblast. A growing number of studies have indicated that bFGF is highly expressed in many kinds of tumor tissues and is closely related to the occurrence and development of tumors. Therefore, bFGF could be a good target for tumor medical treatment. It is also considered as an effective method for tumor therapy by neutralizing bFGF with antibodies and preventing its binding with the receptors.
The clinical study of therapeutic monoclonal antibody has lasted for more than thirty years, and there are more than 400 kinds of therapeutic monoclonal antibodies enter into the clinical stage with commercial support. Nowadays, monoclonal antibodies have been established as a key way for medical treatment directed to varied diseases. In 1995, the first mouse-source monoclonal antibody Edrecolomab was approved in Germany, which was groundbreaking. However, when this mouse-source antibody was applied to human bodies, as a foreign protein, immune response directed to the foreign protein was induced and anti-mouse antibodies (HAMA) were produced. The subsequent studies have demonstrated that this antibody therapy was not as effective as the standard medical treatment. As a result, Edrecolomab exit the market finally. With the development of the molecular biological technology and the clarification of the structure of antibodies, the technology of DNA recombination was applied to modify the antibody, and many kinds of gene engineered antibodies emerged. The initial gene engineered antibodies, including human-mouse chimeric antibodies and remodel antibodies, were for humanized modification in order to decrease the heterogeneity of mouse-monoclonal antibody. The former one was easy to operate but with lower degree of humanization; the latter one was technically difficult but with higher degree of humanization. The appearance of technologies of antibody library have provided new solutions for humanization, however, more mature technologies are required. After that, in order to improve the property of antibodies, various kinds of products such as small molecular antibodies and antibody fusion protein have appeared. Where the small molecular antibodies, as the fragments of the antibody molecules with the function of antigen binding, have the advantages of small molecular weight and strong penetrating ability, and are easy to be constructed and expressed.
Double-stranded antibody (Diabody) is a kind of small molecular antibody, constructed based on the single-stranded antibody, with the characteristics of moderate molecular weight and bivalent state, and is one of the best tumor targeting antibodies. It is also characterized with high penetration ability for tumor tissue and moderate blood clearance rate. Disulfide bond stabilized-diabody (ds-Diabody) is a stable Diabody formed on the basis of Diabody by introducing disulfide bond. Stability of the ds-Diabody is improved, and thus a broadened application perspective is presented. Up to now, there was no paper or patent report about anti-bFGF humanized ds-Diabody.